Is SDHC p.Val82= (c.246C>G) pathogenic?

SDHC p.Val82= (c.246C>G) is classified Likely benign in SDHC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-22). Absent from gnomAD v4.1; Associated with pheochromocytoma/paraganglioma syndrome 3.

What condition is associated with SDHC p.Val82= (c.246C>G)?

SDHC p.Val82= (c.246C>G) is associated with pheochromocytoma/paraganglioma syndrome 3, gastrointestinal stromal tumor, hereditary neoplastic syndrome (ClinVar).

How common is SDHC p.Val82= (c.246C>G) in the general population?

SDHC p.Val82= (c.246C>G) is absent from gnomAD v4.1 (gnomAD).

SDHC p.Val82=

c.246C>G · rs2102370246 · VCV1128589

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

pheochromocytoma/paraganglioma syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.015	GERP -1.8, phastCons 0.76
Overall
CADD	8.082	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SDHC
Protein: p.Val82=
Coding: c.246C>G
MANE Select: NM_003001
dbSNP: rs2102370246
Type: single nucleotide variant
Location: chr1:161356681 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 91.05 · 2 PDB
Residue 82: an α-helix

Full SDHC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pheochromocytoma/paraganglioma syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: gastrointestinal stromal tumor hereditary neoplastic syndrome

Similar variants

SDHC p.Val82Ile Uncertain significance ★★ ⚠ same residue
SDHC p.Val82Phe Uncertain significance ★★ ⚠ same residue
SDHC c.179+1G>C Likely pathogenic ★★ same condition
SDHC c.179+1G>T Likely pathogenic ★★ same condition
SDHC c.180-2A>G Likely pathogenic ★★ same condition
SDHC c.20+1G>T Likely pathogenic ★★ same condition
SDHC c.21-2A>G Pathogenic/Likely pathogenic ★★ same condition
SDHC c.241+1G>A Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/sdhc-p-val82 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown